Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate

Adamik, Barbara; Śmiechowicz, Jakub; Jakubczyk, Dominika; Kübler, Andrzej

doi:10.1097/md.0000000000001085

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…LPS is well known to cause an inflammatory response and organ dysfunction. Moreover, EAA can reflect the severity of sepsis and correlates with clinical outcome [ 19 , 37 , 38 ]. Lastly, EAA is approved by the US FDA and received a CE marked assay.…”

Section: Discussionmentioning

confidence: 99%

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

et al. 2018

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BackgroundRecent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.MethodsWe conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.ResultsFifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.ConclusionPMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial registrationClinicalTrials.gov, NCT02413541. Registered on 3 March 2015. Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2077-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

et al. 2018

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“…Based on the previous researches, it can be mentioned that high concentration of endotoxin in serum may lead to undesirable circumstances, such as the development of septic shock. If it is possible to eliminate the endotoxin, the survival rate will demonstrate the positive tendency to avoid the multiple organ failure [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Morphological Characteristics of the Thymus and Spleen and the Subpopulation Composition of Lymphocytes in Peripheral Blood during Systemic Inflammatory Response in Male Rats with Different Resistance to Hypoxia

Джалилова

Косырева

Diatroptov

et al. 2019

International Journal of Inflammation

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On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.

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“…According to the literature, high levels of serum endotoxin are an unfavorable prognostic criterion for septic shock development, and its therapeutic elimination increases survival, reduces the risk of multiple organ dysfunction, reduces serum C-reactive protein and procalcitonin levels, and increases blood pressure. 47 , 48 …”

Section: Discussionmentioning

confidence: 99%

Sex differences of inflammation in target organs, induced intraperitoneal injection of lipopolysaccharide, depend on its dose

Косырева

Makarova

Kakturskiy

et al. 2018

JIR

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PurposeThe aim of our research was to study sex differences and the severity of inflammatory changes in target organs and the peculiarities of immunological disorders when low and high doses of lipopolysaccharide (LPS) were administered to rats.MethodsMale and female 2- to 3-month-old Wistar rats (200–250 g) were injected intraperitoneally with Escherichia coli LPS in one of two doses: 1.5 or 15 mg/kg. In a day after the LPS injection, we studied endotoxin, corticosterone, sex steroids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity levels in the serum; morphological disorders in the lung, liver, thymus, and spleen; ex vivo production of IL-2, IL-4, tumor necrosis factor (TNF), and interferon γ (IFNγ) by splenic cells activated by ConA; and relative amount of T- and B-lymphocytes in the peripheral blood.ResultsAfter the injection of low-dose LPS, the serum endotoxin level increased only in males and was combined with a more pronounced inflammatory response in the lungs and thymus and an increase in ALT and AST activity levels without any changes in corticosterone level. After the injection of high-dose LPS, the inflammatory and pathological changes in the target organs manifested as severe endotoxemia and sex differences of pathological changes in the lungs and liver were not revealed. The level of production of IL-2, IL-4, IFNγ, and TNF by splenic cells and the number of T-lymphocytes, including cytotoxic cells, in the peripheral blood, decreased in males, which is an evidence of a pronounced suppression of the immune response.ConclusionWe have shown that the morphofunctional changes in the organs of the immune system in females and males, as well as the intensity of the sex differences of inflammation, depend on the severity of systemic inflammatory response, induced by different doses of LPS.

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Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate

Cited by 17 publications

References 29 publications

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

The effect of polymyxin B hemoperfusion on modulation of human leukocyte antigen DR in severe sepsis patients

Morphological Characteristics of the Thymus and Spleen and the Subpopulation Composition of Lymphocytes in Peripheral Blood during Systemic Inflammatory Response in Male Rats with Different Resistance to Hypoxia

Sex differences of inflammation in target organs, induced intraperitoneal injection of lipopolysaccharide, depend on its dose

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